Project Summary Megan Wyatt, MS is a senior Research Specialist in Chrystal Paulos, Ph.D.?s laboratory at the Medical University of South Carolina?s Hollings Cancer Center in the department of Microbiology and Immunology. Dr. Paulos is a well-established cancer immunotherapy researcher, with two current NCI R01 awards, to which Ms. Wyatt has made significant contributions. The first R01 focuses on the inducible costimulator (ICOS), which endows Th17 cells with a superior tumor-killing ability compared to those stimulated with CD28. This R01 aims to determine the mechanism by which ICOS co-stimulation promotes long-term memory and antitumor activity of Th17 cells, by focusing on a core of distinct pathways that may support their persistence, antitumor activity and durable memory generation. The second R01 builds off the Paulos lab?s discovery that human CD4+ T cell which express high levels of the enzyme dipeptidyl peptidase 4 (DPP4), also known as CD26, exhibit superior antitumor activity compared to the traditional Th1, Th2, and even Th17 subsets. The goal of this R01 is to identify the mechanisms by which CD26 regulates the antitumor activity of CD26high CD4+ T cells in vivo, and to clarify the stemness properties of these cells. Ms. Wyatt developed an interest in translational research while completing her Master of Science degree at the College of Charleston. She joined Dr. Paulos? lab after learning of her exciting immunotherapy research. Ms. Wyatt was first assigned to run a P01-derived T cell transduction core, which developed her basic T cell research skills and allowed her to contribute to several different projects with the labs within the P01 grant. Her efforts on this project has been featured in several high-impact publications from both Dr. Paulos? group and other co-investigators. Ms. Wyatt became quite proficient in T cell transduction because of her work in the core, and has been sought out for her expertise by other researchers both at MUSC and externally looking for training and assistance in developing their own transduction protocols. As the P01 ended, Dr. Paulos transitioned Ms. Wyatt to various projects supporting her two R01 grants. Ms. Wyatt has taken on the role of processing and analyzing tumor biopsies obtained from Dr. Paulos? collaborations with physician scientists at MUSC, and using findings from these studies to further the clinical significance of Dr. Paulos? research programs. She also successfully brought CRISPR/Cas9 technology into the lab and was able to knock out CD26 from human T cells, allowing for further exploration into its role in antitumor immunity. Moving forward, Ms. Wyatt will continue to support Dr. Paulos? research programs by conducting critical experiments for the CD26 R01, and providing assistance and guidance for the continuation of the ICOS R01. Her efforts will be essential to the success of these programs, and will be critical for Dr. Paulos to further develop new research programs which will continue to advance and improve adoptive immunotherapy for cancer patients.